Tissue-specific modifier alleles determine Mertk loss-of-function traits
Akalu YT, Mercau ME, Ansems M, Hughes LD, Nevin J, Alberto EJ, Liu XN, He LZ, Alvarado D, Keler T, Kong Y, Philbrick WM, Bosenberg M, Finnemann SC, Iavarone A, Lasorella A, Rothlin CV, Ghosh S. Tissue-specific modifier alleles determine Mertk loss-of-function traits. ELife 2022, 11: e80530. PMID: 35969037, PMCID: PMC9433089, DOI: 10.7554/elife.80530.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityKO miceRetinal pigment epitheliumRetinal degenerationPigment epitheliumPro-inflammatory tumor microenvironmentSyngeneic mouse tumor modelsKO mice displayEarly-onset retinal degenerationSevere retinal degenerationMouse tumor modelsFailure of macrophagesKnockout mouse modelPhotoreceptor outer segmentsMouse modelMice displayTumor modelTumor microenvironmentMacrophage phagocytosisReceptor tyrosine kinasesMiceCritical roleDegenerationMerTKImmunityInflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa
Mercau M, Akalu Y, Mazzoni F, Gyimesi G, Alberto E, Kong Y, Hafler B, Finnemann S, Rothlin C, Ghosh S. Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa. Science Advances 2023, 9: eade9459. PMID: 36662852, PMCID: PMC9858494, DOI: 10.1126/sciadv.ade9459.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumEarly-onset photoreceptor degenerationPR degenerationPigment epitheliumPhotoreceptor degenerationMERTK-associated retinitis pigmentosaJAK1/2 inhibitor ruxolitinibMicroglia activationMonocyte infiltrationInhibitor ruxolitinibMouse modelInflammationLoss of functionDefective phagocytosisInflammation drivesRetinitis pigmentosaDegenerationHypomorphic expressionMiceEpitheliumPhagocytosisRuxolitinibPigmentosaSeverity